title: Parenteral is more efficient than mucosal immunization to  induce regression of human papillomavirus-associated genital  tumors.
abstract: Cervical cancer is a public health concern as it represents the second cause of cancer death in women worldwide. High-risk human papillomaviruses (HPV) are the etiologic agents, and HPV E6 and/or E7 oncogene-specific therapeutic vaccines are under development to treat HPV-related lesions in women. Whether the use of mucosal routes of immunization may be preferable for inducing cell-mediated immune responses able to eradicate genital tumors is still debated because of the uniqueness of the female genital mucosa (GM) and the limited experimentation. Here, we compared the protective activity resulting from immunization of mice via intranasal (i.n.), intravaginal (IVAG) or subcutaneous (s.c.) routes with an adjuvanted HPV type 16 E7 polypeptide vaccine. Our data show that s.c. and i.n. immunizations elicited similar frequencies and avidity of TetE71CD81 and E7-specific Interferon-gamma-secreting cells in the GM, whereas slightly lower immune responses were induced by IVAG immunization. In a novel orthotopic murine model, both s.c. and i.n. immunizations allowed for complete long-term protection against genital E7-expressing tumor challenge. However, only s.c. immunization induced complete regression of already established genital tumors. This suggests that the higher E7-specific systemic response observed after s.c. immunization may contribute to the regression of growing genital tumors, whereas local immune responses may be sufficient to impede genital challenges. Thus, our data show that for an efficiently adjuvanted protein-based vaccine, parenteral vaccination route is superior to mucosal vaccination route for inducing regression of established genital tumors in a murine model of HPV-associated genital cancer.
authors.affiliation: Department of Urology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
authors.forename: Loane
authors.initials: L
authors.lastname: Decrausaz
authors.forename: Sonia
authors.initials: S
authors.lastname: Domingos-Pereira
authors.forename: Mélanie
authors.initials: M
authors.lastname: Duc
authors.forename: Martine
authors.initials: M
authors.lastname: Bobst
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: John T
authors.initials: JT
authors.lastname: Schiller
authors.forename: Patrice
authors.initials: P
authors.lastname: Jichlinski
authors.forename: Denise
authors.initials: D
authors.lastname: Nardelli-Haefliger
mesh_terms: D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D007263:Infusions, Parenteral; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology; D030361:Papillomavirus Infections / Q000628:therapy*; D053918:Papillomavirus Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy* / Q000821:virology; D014611:Vaccination / Q000379:methods*
chemical_list: D019496:Cancer Vaccines; D050725:Papillomavirus E7 Proteins; D053918:Papillomavirus Vaccines